DESCRIPTION (Applicant's Abstract) Patients with diabetic nephropathy experience markedly increased rates of morbidity and mortality due to arteriosclerotic cardio- vascular disease [CVD]. Established arteriosclerotic risk factors such as age, sex, cigarette smoking, hypertension, and dysilpidernia do not account adequately for this excess CVD risk. Prospective data from general populations, and much more limited findings from both diabetic cohorts. and cohorts with chronic renal disease, have linked elevated levels of total hornocysteine (tHcy) and C-reactive protein (CRP) to arteriosclerotic CVD morbidity and mortality. Determination of baseline serum tHcy and CRP concentrations in the Irbesartan Type 2 Diabetic Nephropathy Trial (IDNT) cohort affords a truly unique opportunity to evaluate the potential independent relationship between these putative CVD risk factors and subsequent CVD morbidity and mortality, in this patient population. Specific Aim I (Longitudinal analyses): To evaluate the potential "Independent" relationship* between baseline concentrations of serum total hornocysteine (tHcy) and C-reactive protein (CRP) in the full IDNT cohort, and subsequent:pooled CVD morbidity and mortality (primary analysis). total mortality, (*after multivariable -adjustment for the established predictors of CVD morbidity/ mortality, and total mortality). Specific Aim 2 -(Cross- sectional analyses): To assess baseline serum total hornocysteine (tHcy) and C-reactive protein (CRP) concentrations in the full IDNT collort, in relation to potential baseline determinants of these analytes, including: B-vitamin status; age and gender; renal function indices, i.e. both creatinine-based GFR estimates, and proteinuria; indices of glycernia, prevalent cardiovascular disease (CVD), traditional CVD risk factors (i.e., in particular, smoking, blood pressure, and total cholesterol/HDL cholesterol ratio). Using proportional hazards modeling, with complete data available from 1650 total subjects, we will have 83.0% power at a two-tailed alpha of 0.05 to detect a relative risk estimate (hazards ratio) for total CVD Occurrence of 1.4, comparing quartile 4, to quartiles 1-3 of either tHcv or CRP. Our prospective findings will help elucidate whether measurement of these Putative CVD risk factors may provide useful Information for CVD risk assessment in mild to moderate renal insufficiency due to diabetic nephropathy, specifically.